Matrix Assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS) has a unique potential for polynucleotide analysis beyond the limits of other soft ionization methods, because of its ability to introduce large oligonucleotide molecules into gas phase, with minimum sample degradation. We have proposed a tunable infrared laser to expand this capability, by exploring a variety of desorption matrices and protocols for overcoming low ionization efficiency and metastable decay encountered with conventional UV-MALDI-MS. In Phase I, we have built a novel, tunable, IR source consisting of an optical parametric oscillator (OPO) pumped by a tunable Cr:LiSAF laser, and obtained high resolution delta m is less than 15 at mu/z=5735, S/N is greater than l50) IR-MALDI mass spectra of DNA, protein and peptides with this laser. Following this successful feasibility study, we will build, in Phase II, a prototype compact IR- MALDIMS instrument having unique potential to analyze large biomolecules at high throughput. This instrument will integrate a Delayed-ion Extraction T0F-MS with diode-pumped Cr:LiSAF/0P0 laser widely tunable from 2.7 to 3.4 mu, which can excite O-H, C-H and N-H bonds in wide range of matrices. Using this instrument DNA analysis and optimization of MALDI techniques will be performed. This work will help develop new features of MALDI-MS with fundamental impact on biomedical analysis. PROPOSED COMMERCIAL APPLICATION: Many medical and clinical applications such as, analysis of DNA & RNA, PCR fragments, proteins and peptides, are envisaged. The DNA diagnostics application will enable commercialization of compact, cost effective, MALDI-MS systems for use in health-care, medicine, agriculture, and environmental monitoring fields.